Search Results (1,314)

This study reports the development of a fiber-optic localized surface plasmon resonance (FO-LSPR) sensor incorporating a three-dimensional micropillar array functionalized with gold nanoparticles. The micropillar structures were fabricated on the fiber facet using a single-mask imprint lithography process, followed by nanoparticle immobilization to create a composite plasmonic surface. Compared with flat polymer-coated fibers, the micropillar array markedly increased the effective sensing surface and enhanced light trapping by providing anti-reflective conditions at the interface. Consequently, the sensor demonstrated superior performance in refractive index sensing, yielding a sensitivity of 4.54 with an R² of 0.984, in contrast to 3.13 and 0.979 obtained for the flat counterpart. To validate its biosensing applicability, Interleukin-8 (IL-8), a cancer-associated cytokine, was selected as a model analyte. Direct immunoassays revealed quantitative detection across a broad dynamic range (0.1–1000 pg/mL) with a limit of detection of 0.013 pg/mL, while specificity was confirmed against non-target proteins. The proposed FO-LSPR platform thus offers a cost-effective and reproducible route to overcome the surface-area limitations of conventional designs, providing enhanced sensitivity and stability. These results highlight the potential of the micropillar-based FO-LSPR sensor for practical deployment in point-of-care diagnostics and real-time biomolecular monitoring. Full article

Background: Recombinant monoclonal antibodies (mAbs) represent the fastest-growing sector of the biopharmaceutical industry, with their efficient expression being a key technological factor for scalability. Objectives: In this study we compared the performance of two bicistronic vectors, which alternate the positions of the light and heavy chain coding genes, employing a wild-type Encephalomyocarditis virus (EMCV) IRES functional element to drive expression of the second gene. Methods: Using two neutralizing anti-SARS-CoV-2 IgG1 antibodies as model molecules, we conducted transient transfections in the commercially available ExpiCHO^TM platform. Following protein A affinity purification and quantification, vectors positioning the light chain as the first cistron consistently yielded higher expression levels than those with the heavy chain upstream. To confirm the quality attributes of the mAbs, we applied a comprehensive analytical workflow, including SDS-PAGE and Western blot for molecular mass and purity, circular dichroism for secondary structure, intrinsic tryptophan fluorescence for tertiary structure, and SEC-HPLC for quaternary structure and aggregate detection. Additionally, we assessed binding affinity to the target using spot blot and surface plasmon resonance, analyzed N-glycosylation profiles by HILIC-HPLC and mass spectrometry, and examined molecular structure by transmission electron microscopy. Results and Conclusions: Together, these results provide insight into the impact of gene positioning within bicistronic vectors on mAb expression efficiency and quality, supporting optimization strategies for scalable recombinant antibody production. Full article

This work proposes a novel polarization-maintaining hollow-core anti-resonant fiber structure characterized by high birefringence and low transmission loss. To address the inherent trade-off between birefringence and confinement loss, a Pareto-front-based multi-objective optimization algorithm is introduced into the geometrical design of the ARF. The optimal fiber design achieves a birefringence exceeding $1\times {10}^{-4}$ and a confinement loss of approximately 1 dB/m at the telecommunication wavelength of 1.55 $\mathsf{\mu }$m. In particular, the asymmetric wall thickness configuration further improves the trade-off, enabling confinement loss as low as 0.15 dB/m while maintaining birefringence on the order of $1\times {10}^{-4}$. This approach significantly reduces computational cost and exhibits strong potential for applications in polarization-maintaining communications, precision sensing, and high-power laser delivery. Full article

Background: Folic acid (FA), also known as vitamin B9, functions as a co-factor in many cellular processes. Ultraviolet radiation (UV) has been shown to cause the formation of free radicals, and chronic exposure of the skin to UV radiation has been demonstrated to result in many adverse effects. Skin protection against harmful environmental factors is one of the aims of cosmetic products. One such substance is folic acid. However, aqueous FA solutions decompose after exposure to UV radiation, and the decomposition products can exhibit variable pro/anti-oxidative roles depending on the cell type and its environment. Objectives: The objective of the present study was to demonstrate the effectiveness of folic acid as a UV-protective agent in vitro cell culture model. Methods: The experimental model comprised an in vitro culture of normal human fibroblasts derived from adult skin (NHDF-Ad). Paramagnetic electron resonance (EPR) was used to assess the interaction of folic acid with free radicals after exposure to UV radiation. RT-qPCR was utilized to evaluate the impact of ultraviolet (UV) radiation on the expression of selected cell cycle regulatory genes (CCND1, P53, BAX, and BCL-2) in vitro cultured fibroblasts that were protected by folic acid. Results: EPR studies revealed the antioxidant properties of folic acid. Free radical forms of folic acid are induced during UV irradiation. The strong effect of UV irradiation on interactions of folic acid with free radicals was observed. The interaction was found to be weaker for the irradiated samples. Molecular studies have demonstrated a decline in the BAX/BCL-2 ratio in cells that have been treated with folic acid and exposed to UV radiation in comparison to the BAX/BCL-2 ratio observed in cells that have been exposed exclusively to UV radiation and not treated with folic acid. Conclusions: Whilst molecular and EPR studies both confirm the effectiveness of folic acid as a UV-protective ingredient in cosmetics and pharmaceutical products, further research in this area is required. Full article

Avicennia marina, commonly known as the grey mangrove, is a salt-tolerant species widely distributed in coastal and estuarine ecosystems. Traditionally, it has been used in folk medicine to treat skin diseases, rheumatism, and ulcers due to its anti-inflammatory and antimicrobial properties. However, comprehensive studies on the chemical constituents and their pharmacological effects remain limited. The dried powder of the aerial parts of A. marina (3.6 kg) was successfully extracted three times with methanol (20 L × 3, each for 2 h) using a multifunctional ultrasonic cleaner operated at 25 °C with a 50% amplitude setting. In this study, the methanolic extract of the aerial parts of A. marina led to the isolation of eight compounds, including two previously unreported iridoid glycosides—avicenosides A and B (1 and 2)—and six known compounds: techtochrysin (3), 7,4′-di-O-methyl-apigenin (4), luteolin (5), kaempferol (6), trans-caffeic acid (7), and 3,4-dihydroxybenzoic acid (8). Their chemical structures were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and compared with previously published data. Moreover, the absolute configuration of the sugar moieties in the new compounds was also identified. All isolated compounds were evaluated for their cytotoxicity against HepG2 and A549 cancer cell lines. The results indicate potential cytotoxicity of the secondary metabolites from A. marina and provide evidence of their promising role as lead compounds for the development of novel anticancer agents. Full article

This study employed an integrated computational approach to discover novel nucleoprotein (NP) inhibitors for influenza A virus (IAV). Beginning with virtual screening of over 10 million compounds using Schrödinger’s Glide module (HTVS, SP, XP docking), the workflow identified promising candidates with favorable binding energies. Subsequent molecular mechanics/generalized born surface area (MM-GBSA) calculations and 100 ns molecular dynamics (MD) simulations prioritized 16 compounds for experimental validation. Surface plasmon resonance (SPR) assays revealed that compounds 8, 13, and 14 demonstrated superior target engagement, showing equilibrium dissociation constants (K_D) of 7.85 × 10⁻⁵ M, 3.82 × 10⁻⁵ M, and 6.97 × 10⁻⁵ M, respectively. Molecular dynamics, alanine scanning mutagenesis, and quantum mechanics/molecular mechanics (QM/MM) analysis were conducted to analyze the binding modes, providing a reference for the design of subsequent compounds. These findings validate the efficacy of structure-based virtual screening in identifying high-affinity NP inhibitors and provide insights for the development of broad-spectrum anti-influenza therapeutics. Full article

Dysferlin direct protein–protein interactions (PPI) previously have been elucidated with surface plasmon resonance (SPR) and predicted to underlie membrane repair in mechanotransducing myofibrils. In mechanotransducing inner ear hair cells, dysferlin is detected with Z-stack confocal immunofluorescence in the stereocilia and their inserts in the tectorial membrane (TM) co-localizing with FKBP8, consistent with the SPR determination of tight, positively Ca²⁺-dependent interaction. FKBP8, a direct binding partner of mechanotransducing TMC1, when overexpressed, evokes an elevation in anti-apoptotic BCL2, inhibition of ryanodine receptor (RYR) activity, and a consequent reduction in Ca²⁺ release. RYR3 has now been immunolocalized to the tip of the TM in close association with a third-row outer hair cell (OHC) stereociliary BCL2-positive insertion. Dysferlin, annexin A2, and Alzheimer’s proteins BACE1 and amyloid precursor protein (APP) are also accumulated in these stereociliary insertions. RYR2 and RYR1 have been immunolocalized to the TM core, in position to influence TM Ca²⁺. Dysferlin PPI pathways also intersect with AD protein pathways in the spiral ganglion (SG). Dysferlin segregates with FKBP8, BACE1, and RYR3 in the interiors of SG type I cell bodies. RYR1, RYR2, PSEN1, BCL2, and caspase 3 are primarily confined to plasma membrane sites. RYR3 pathways traverse the plasma membrane to the cell body interior. Western analysis of dysferlinopathy proteins links FKBP8 and BCL2 overexpression with RYR inhibition, indicative of dysferlin targets that are ameliorative in AD. Full article

Autopsy studies have shown that Alzheimer’s disease (AD) often coexists with cerebrovascular injury, affecting cognitive outcomes and the effectiveness of anti-amyloid-beta (Aβ) drugs. No fluid biomarkers of cerebrovascular injury have been identified yet. We investigated the association between white matter hyperintensities (WMH) severity and fluid biomarkers, including cerebrospinal fluid (CSF) neurofilament light chain and plasma placental growth factor (PlGF) levels. This study included 242 patients from memory clinics. Magnetic resonance imaging (MRI), CSF, and plasma samples were collected. Patients were classified as AD+ or non-AD based on the CSF Aβ42/Aβ40 ratio. In the discovery cohort (79 AD+ and 20 non-AD patients with 3D-T1 images), we analyzed the association between WMH volume and plasma PlGF. In the validation cohort (54 AD+ patients without 3D-T1 images), we analyzed the association between WMH grading and plasma PlGF. Among AD+ patients in the discovery cohort, plasma PlGF levels remained significantly associated with WMH volume and grading after adjusting for age, sex, and global cognition. Among the AD+ patients in the validation cohort, the high-PlGF (above median) group had significantly greater WMH volumes and a higher number of patients with a high WMH grading than the low-PlGF (below median) group. Plasma PlGF is a promising marker of cerebrovascular injury in AD. Full article

Alveolar echinococcosis (AE) is a zoonotic disease caused by the larval form of the tapeworm Echinococcus multilocularis, which is considered one of the most dangerous parasites for humans. E. multilocularis infections are most frequently observed in forestry workers, farmers, hunters, berry harvesters, and workers employed in animal shelters. The subject of this study was a four-year follow-up profile of cytokines, including tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-4 (IL-4), and interleukin-10 (IL-10), in a patient with advanced liver alveolar echinococcosis and non-optimal antiparasitic treatment. Ultrasound, computed tomography (CT) of the abdomen, X-ray, CT of the chest, and magnetic resonance imaging (MRI) of the head were performed during the observation and treatment of the AE patient. After antiparasitic treatment was initiated, decreased activity of the gamma-glutamyl transpeptidase (GGTP), decreased serum concentrations of immunoglobulin E, C-reactive protein (CRP), and the pro-inflammatory cytokines TNFα, IL-1, and IL-6 were observed, as well as slightly increased levels of the anti-inflammatory cytokines (IL-4 and IL-10). Conclusions. During a four-year follow-up in a patient with advanced hepatic alveolar echinococcosis and non-optimal antiparasitic treatment, a decrease in proinflammatory cytokines (TNFα, IL-1β, IL-6) and a slight increase in anti-inflammatory cytokines (IL-4, IL-10) were detected. A better understanding of cytokine regulation in infectious diseases may be important to the development of new therapeutic strategies aimed at antiparasitic treatment. We suggest that broad initiatives (preferably at the local community level) should be implemented to raise awareness of the threat of alveolar echinococcosis and methods for avoiding E. multilocularis infection. Full article

Anti-resonant hollow-core fibers (AR-HCFs) are emerging as highly promising candidates for high-power laser transmission and low-loss optical communication. Despite their advantages, issues such as scattering loss and core-mode instability remain significant obstacles for their practical implementation. In this study, we propose a novel hybrid fiber structure, the nano-core plus node-free anti-resonant hollow-core fiber (NPNANF), which integrates a solid, high-index nano-core within a six-tube node-free anti-resonant cladding. This hybrid design effectively enhances optical confinement while minimizing scattering losses, without relying solely on anti-resonant guidance. Numerical simulations employing the beam propagation method (BPM) and finite element analysis (FEA) demonstrate that an optimal nano-core diameter of 600 nm leads to a remarkable reduction in transmission loss to 0.025 dB/km at 1550 nm, representing a 99.8% decrease compared to conventional NANF designs. A comprehensive loss model is developed, incorporating contributions from confinement, scattering, and absorption losses in both the hollow cladding and the solid core. Parametric studies further illustrate the tunability of the fiber’s design for various high-performance applications. The proposed NPNANF achieves an ultra-low transmission loss of 0.025 dB/km, representing a >99.8% reduction compared to conventional NANF, while confining more than 92% of optical power within the nano-core. Its resistance to bending loss, strong modal stability, and balance between hollow-core and solid-core guidance highlight the advantages of NPNANF for long-haul optical communication and high-power photonics. Full article

Background/Objectives: This study identifies novel dihydroorotate dehydrogenase (DHODH) inhibitors exhibiting potent broad-spectrum antiviral agents, particularly against influenza A virus (A/PR/8/34(H1N1)) and SARS-CoV-2. Methods: Structure-based virtual screening of 1.6 million compounds (ChemDiv and TargetMol databases) yielded 10 candidates, with compounds 6, 9, and 10 demonstrating significant anti-influenza activity (IC₅₀ = 4.85 ± 0.58, 7.35 ± 1.65, and 1.75 ± 0.28 μM, respectively). Building on these, molecular hybridization principles and scaffold hopping principles were applied to design and synthesize six novel compounds (11–16) through cyclization, coupling, and carboxylate deprotection. Prior to subsequent biological assays, the molecular structures of each compound were elucidated by NMR spectroscopy and MS. Their antiviral activities were subsequently assessed against both influenza virus and SARS-CoV-2. The compound 11, demonstrating the most potent antiviral activity, was further subjected to surface plasmon resonance (SPR) analysis to assess its binding affinity for human DHODH. Results: Compound 11 emerged as the most potent DHODH inhibitor (K_D = 6.06 μM), exhibiting superior broad-spectrum antiviral activities (IC₅₀ = 0.85 ± 0.05 μM, A/PR/8/34(H1N1); IC₅₀ = 3.60 ± 0.67 μM, SARS-CoV-2) to the reported DHODH inhibitor (Teriflunomide, IC₅₀ = 35.02 ± 3.33 μM, A/PR/8/34(H1N1); IC₅₀ = 26.06 ± 4.32 μM, SARS-CoV-2). Mechanistic evaluations via 100 ns MD simulations and QM/MM calculations revealed stable binding interactions, particularly hydrogen bonds with GLN47 and ARG136, while alanine scanning mutagenesis confirmed these residues’ critical roles in binding stability. Conclusions: This work identifies compound 11 as a potent broad-spectrum antiviral compound, offering a promising strategy for broad-spectrum antiviral therapy against RNA viruses by depleting pyrimidine pools essential for viral replication. Full article

Background/Objectives: Selective inhibition of bacterial virulence factors is a promising strategy to convert pathogenic bacteria into non-pathogenic commensals, circumventing the challenge of antibiotic resistance. This approach enables the host immune system to eliminate virulence-attenuated pathogens. Methods: In this study, we evaluated the effects of Lindera obtusiloba Blume extract and cinnamtannin B1, the active component of the ethyl acetate fraction, on the type III secretion system (T3SS) of Yersinia enterocolitica. Results: The ethyl acetate fraction, at 100 mg/L, effectively suppressed all three T3SS components—the flagellar, Ysa, and Ysc T3SSs. Cinnamtannin B1, isolated from the ethyl acetate fraction through separation and identified through nuclear magnetic resonance spectrometer analysis, significantly inhibited flagellar and Ysa T3SS secretion, while selectively inhibiting expression of key effector proteins YopH and YopO in the Ysc T3SS. Additionally, cinnamtannin B1 reduced Y. enterocolitica-induced RAW 264.7 macrophage mortality and prevented poly (ADP-ribose) polymerase degradation, a marker of apoptosis. Conclusions: These findings suggest cinnamtannin B1 from L. obtusiloba as a selective T3SS-targeting compound with mechanistic potential for anti-virulence intervention. Further in vivo validation will be necessary to evaluate its therapeutic applicability. Full article

Gastroesophageal reflux disease (GERD) is associated with symptoms such as heartburn, resulting from gastric content reflux. Alginate-based raft-forming gel formulations represent a non-pharmacological strategy for GERD management by forming a floating gel barrier in the stomach. This study evaluated three commercial anti-reflux oral gel systems under simulated fed-state gastric conditions, using in vitro magnetic resonance relaxometry techniques. Magnetic resonance imaging (MRI) was performed in 0.01 M hydrochloric acid (HCl) to visualize gel raft formation, spatial structure, and spatial distribution of effective T₂ relaxation time. Nuclear magnetic resonance (NMR) relaxometry in 0.01 M deuterium chloride (DCl) measured T₁ and T₂ relaxation times of the protons that were initially included in the preparation to assess its molecular mobility within the gel matrix. Two formulations formed floating, coherent gels, whereas the remaining one exhibited only polymer swelling without flotation. In one case, relaxometry data revealed a solid-like component that can be detected, indicating enhanced mechanical stability. The performance of each formulation was influenced by interactions among alginate, bicarbonates, and calcium ions, which determined gel consistency and flotation behavior. MRI and NMR relaxometry in vitro provide valuable non-invasive insights into the structural and functional behavior of alginate-based gel formulations. This approach supports the rational design of advanced gel-based therapies for GERD by linking molecular composition with in situ performance. Full article

Background: Cardiac involvement is a major cause of morbidity and mortality in systemic sclerosis (SSc). Autoantibodies may help identify patients at increased cardiovascular (CV) risk. This systematic review aimed to assess the predictive value of classical and emerging SSc-related autoantibodies for cardiac involvement and their integration with imaging and cardiac biomarkers. Methods: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library up to 16 July 2025. Studies were included if they reported associations between specific autoantibodies and cardiac outcomes (e.g., myocardial fibrosis, conduction abnormalities, arrhythmias, ventricular dysfunction) in adult patients with SSc. Data extraction and quality assessment followed PRISMA 2020 guidelines. The review protocol was registered in PROSPERO (registration ID: CRD420251107782). Results: Anti-topoisomerase I antibodies were associated with myocardial fibrosis, subclinical systolic and diastolic dysfunction, elevated cardiac biomarkers, and pathological findings on cardiac magnetic resonance imaging. Anti-centromere antibodies were linked to conduction system abnormalities, particularly among older individuals. Anti-RNA polymerase III and anti-U3 ribonucleoprotein antibodies correlated strongly with arrhythmias and pericardial involvement. Novel autoantibodies, such as anti-heart antibodies and anti-intercalated disk antibodies, were linked to early myocardial injury, although their clinical utility requires further validation. Across studies, serological markers alone were insufficient to predict cardiac outcomes without concurrent imaging or biomarker evaluation. Conclusions: Autoantibody profiling plays an important role in CV risk stratification in SSc. Combining serological testing with cardiac biomarkers and advanced imaging enhances early detection and supports individualized monitoring. Further longitudinal studies are needed to validate predictive models and optimize patient outcomes. Full article

To address the issues of limited orbital angular momentum (OAM) mode count, poor transmission quality, and complex cladding structures in ring-core photonic crystal fibers, a novel OAM-supporting ring-core anti-resonant photonic crystal fiber is designed. This fiber features a high-index-doped ring-core surrounded by a three-layer anti-resonant nested tube cladding. Numerical simulations based on the finite element method indicate that the designed fiber has the ability to reliably transmit up to 90 OAM modes within the wavelength range of 1530–1620 nm. Additionally, this fiber demonstrates outstanding performance characteristics, achieving a peak effective refractive index difference of 0.0041 while maintaining remarkably low confinement loss between 10⁻¹² dB/m and 10⁻⁸ dB/m. The minimum effective mode field area is 101.41 μm², and the maximum nonlinear coefficient is 1.05 W⁻¹·km⁻¹. The dispersion is flat, with a minimum dispersion variation of merely 0.5394 ps/(nm·km). The mode purity is greater than 98.5%, and the numerical aperture ranges from 0.0689 to 0.089. The designed OAM-supporting ring-core anti-resonant photonic crystal fiber has broad application prospects in long-haul optical communication and high-speed data transmission. Full article